Corey Cavanaugh, DO, is an academic nephrologist at the Cleveland Clinic. 

Corey Cavanaugh, DO

2 IgA Nephropathy Experts Explain Clues For Early Intervention and Diagnosis

Two experts in nephrology are emphasizing the importance of identifying early clinical signs of IgA nephropathy (IgAN), often described as a silent disease.

“Clinicians should pay close attention to hypertension—especially in younger patients—and microscopic hematuria, again particularly in younger individuals,” said Corey Cavanaugh, DO, an academic nephrologist at the Cleveland Clinic, in an interview with HCPLive. “This is largely a young person’s disease, and it can be easy to explain these findings away or attribute them to something other than IgA nephropathy, since they’re relatively nonspecific. That’s why it requires a high index of suspicion and an astute clinician, particularly among non-nephrologists. It can be very subtle.”

Since these early findings are often attributed to benign or transient causes, diagnosis can often wind up delayed. By the time a majority of patients are diagnosed with IgAN, 50% to 75% have already progressed to chronic kidney disease (CKD) stage 3. At this point, eGFR falls below 60 mL/min/1.73 m² and structural kidney damage becomes irreversible, underscoring a need for earlier intervention. 

IgAN’s symptoms can be clinically silent before they progress to worsened stages, including non-visible hematuria, proteinuria, impaired kidney function, or hypertension. In one recent analysis, approximately 60% of IgAN cases were detected incidentally through hematuria or proteinuria identified on routine urinalysis. As a result, clinicians must rely heavily on measurable markers to assess disease activity and progression risk, with proteinuria remaining one of the most important indicators of long-term outcomes.

“When it comes to prognostication, we have to integrate clinical markers—serum creatinine, proteinuria, and hypertension—with demographic factors, including age and ethnicity, as well as histologic markers,” said Abdallah Geara, MD, Associate Professor of Clinical Medicine at the University of Pennsylvania, in an interview with HCPLive. “Bringing these together allows us to create a risk assessment for each patient, which then guides the next step in treatment. As therapies continue to evolve, the treatment algorithm has changed quite a bit over the last few years and will likely keep evolving.”

As the IgAN treatment landscape is experiencing a therapeutic revolution, this approach to risk stratification is becoming increasingly important. With 5 recently approved agents across distinct mechanistic pathways, therapeutic options are no longer the primary limitation. Instead, the focus is shifting toward earlier identification and precise risk assessment to ensure these therapies are deployed at a stage when they can have the greatest impact.

Editor’s Note: Abdallah reports relevant disclosures with Amgen, GlaxoSmithKline, Novartis, and others. Cavanaugh reports relevant disclosures with Otsuka Pharmaceutical Co, Novartis Pharmaceutical Corporation, Travere Therapeutics, and Vera Therapeutics.

Stoneman S, Teh JW, O’Shaughnessy MM. IgA nephropathy in adults. 

. Published online January 26, 2026. doi:10.1001/jama.2025.25020

Kidney Disease: Improving Global Outcomes (KDIGO) Glomerular Diseases Work Group. KDIGO 2021 clinical practice guideline for the management of glomerular diseases. 

. 2021;100(4S):S1-S276. doi:10.1016/j.kint.2021.05.021

Videos

Corey Cavanaugh, DO, and Abdallah Geara, MD, separately share their perspectives on the clinical clues for IgAN diagnosis, including hypertension and microscopic hematuria.

Who Gets What, When? Navigating Therapy Selection in IgA Nephropathy, With Corey Cavanaugh, DO

 has considerably expanded recently, clinicians continue to navigate how best to select and sequence these emerging therapies for their patients.

New breakthrough developments have brought treatment options well beyond traditional approaches, such as corticosteroids and supportive care, now encompassing complement inhibitors and APRIL/BAFF-targeting agents.

“On the immunosuppressive side, we still have corticosteroids, we still have targeted release… sort of the newer kids on the block, if you will, are the complement inhibitor… and then our anti April therapies that are numerous and rolling out. Those are the major ones we're fixating on,” ​​said Corey Cavanaugh, DO, an academic nephrologist at the Cleveland Clinic, in an interview with HCPLive. “The major question is, who gets what and when, and that still is… this is a matter of, just to be clear right off the bat, this is not necessarily evidence-based. This is all just opinion-based.”

2025 Kidney Disease: Improving Global Outcomes (KDIGO) 

updated IgAN guidelines marked a conceptual shift, recommending clinicians to initiate therapies targeting pathogenic IgA production simultaneously with those addressing the consequences of existing nephron loss, a dual-track approach departing from the traditional stepwise model. The guidelines also introduced a more stringent proteinuria target, with the goal of achieving <0.3 g/d.

 proteinuria and eGFR remain the only validated biomarkers 

to guide therapy selection in the continuously expanding therapeutic landscape. Combination regimens may offer additive benefits, but supporting evidence is still emerging, and there is no existing evidence-based framework for sequencing decisions yet.

Meaningful progress toward personalized therapy in IgAN will depend on identifying biomarkers which can guide which patients are most likely to benefit from complement inhibition, APRIL blockade, or targeted intestinal therapy with Nefecon.

“My personal preference is to avoid steroids as much as I can, whether it be targeted release or oral systemic corticosteroids. That's just my personal preference. When we have a steroid-sparing option, I'm going to choose it. Young people don't like steroids… like anyone else.”

Current evidence supports guideline recommendations to avoid corticosteroid therapy in those with an eGFR <30 mL/min/1.73 m² and the suggestion to exercise cautiously in individuals at high risk of developing corticosteroid-related side effects, such as those with diabetes mellitus, obesity, latent infections, active peptic ulceration, uncontrolled psychiatric illness, and severe osteoporosis.

Editor’s Note: Cavanaugh reports relevant disclosures with Otsuka Pharmaceutical Co, Novartis Pharmaceutical Corporation, Travere Therapeutics, and Vera Therapeutics.

Floege J, Barratt J, Cook HT, et al. Executive summary of the KDIGO 2025 Clinical Practice Guideline for the Management of Immunoglobulin A Nephropathy (IgAN) and Immunoglobulin A Vasculitis (IgAV). 

https://doi.org/10.1016/j.kint.2025.04.003

In a rapidly evolving therapeutic landscape, how can clinicians make decisions to personalize IgAN care?

Even Routine Urinalysis Can Reveal Hidden IgAN In Young Patients, With Corey Cavanaugh, DO

 often silent presentation, clinicians should remain vigilant for hypertension and microscopic hematuria during routine evaluations, particularly among younger adults.

“It's not unusual that patients get a life insurance policy evaluation and get screened for hematuria, or they're getting some sort of surgery and a pre-op evaluation. Clinicians should pay close attention to hypertension and microscopic hematuria, especially in young people. Of course, this is a young person's disease,” said Corey Cavanaugh, DO, an academic nephrologist at the Cleveland Clinic, in an interview with HCPLive. “It can be easy to talk away these things, or at least give them a reasonable explanation that isn't IgAN, because they're non-specific features, so it requires a high index of suspicion and an astute clinician for the non-nephrologist, especially.”

The majority of patients with IgAN present with non-visible hematuria, proteinuria, impaired kidney function, or hypertension, features often classified as silent symptoms. A recent study found that approximately 60% of IgAN cases were detected incidentally through hematuria or proteinuria on urinalysis.

Since many early symptoms are subtle, clinicians often rely on measurable markers to assess disease activity and progression risk. Among these, proteinuria remains one of the most important indicators for identifying patients at greater risk of disease progression and kidney failure.

“The most powerful prognostic clinical indicators are few, actually, but the most powerful one I tend to adhere to is still proteinuria,” said Cavanaugh.

Proteinuria often serves as a key trigger for further diagnostic evaluation. According to the 2025 

Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guidelines for IgAN and IgA Vasculitis (IgAV)

, clinicians should perform a kidney biopsy to confirm diagnosis in patients with suspected IgAN and persistent proteinuria ≥0.5 g/day.

Early detection is increasingly important as the therapeutic landscape for IgAN expands. New targeted treatments, including selective corticosteroids, dual endothelin-angiotensin blockers, and emerging complement inhibitors, offer opportunities to slow disease progression and reduce proteinuria.

Stoneman S, Teh JW, O’Shaughnessy MM. IgA Nephropathy in Adults. JAMA. Published online January 26, 2026. doi:

Floege J, Barratt J, Cook HT, et al. Executive summary of the KDIGO 2025 Clinical Practice Guideline for the Management of Immunoglobulin A Nephropathy (IgAN) and Immunoglobulin A Vasculitis (IgAV). Kidney international. 2025;108(4):548-554. doi:

Even Routine Urinalysis Can Reveal Hidden IgA Nephropathy, Especially in Young Adults

Unmet Needs and Unanswered Question in C3G

, Shikha Wadhwani, MD, MS, Anuja Java, MD, and Corey Cavanaugh, DO, reflect on the promise and challenges of integrating FDA-approved therapies like pegcetacoplan and iptacopan into clinical practice for patients with 

C3 glomerulopathy (C3G) and immune complex–mediated membranoproliferative glomerulonephritis (IC-MPGN)

A New Era for C3G Treatment with Pegcetacoplan

Navigating Targeted Therapies for C3 Glomerulopathy

Understanding Pegcetacoplan in C3G with VALIANT Data

Approaching Incident C3G in an Era of Targeted Therapies

Unmet Needs and Unanswered Questions in C3G

While both approvals mark a major step forward, the panel is candid about the real-world barriers that still stand in the way, with access to therapy chief among them. Cavanaugh emphasizes the logistical and financial hurdles in securing these high-cost drugs, even for young patients who may urgently need them. He anticipates that larger academic centers and designated centers of excellence will play a crucial role in helping regional providers navigate these complexities and secure timely treatment.

Java shares the same enthusiasm about having disease-targeted options but flags the persistent frustrations of insurance denials, even for long-established complement inhibitors. Both she and Cavanaugh express ongoing uncertainty about how to apply trial findings to the diverse patient populations seen in practice, especially those with atypical presentations or no clear genetic or functional complement driver. They also grapple with how best to manage transplant patients, many of whom may be on anti-C5 therapy already and raise questions about whether upstream inhibition might offer better long-term outcomes.

The discussion also touches on the lack of predictive tools to determine who will respond to therapy, who will progress, and when and how often repeat biopsies should be performed in seemingly stable patients.

As Wadhwani notes in closing, nephrologists are entering a new era in C3G marked by momentum, collaboration, and the opportunity to finally align pathophysiology with treatment. The panel agrees the key now is to ensure that the promise of clinical trial data translates into equitable, durable outcomes for patients across practice settings.

 is an associate professor of Medicine and the vice chair of Clinical Research at the University of Texas Medical Branch. Wadhwani, who is the co-host of HCPLive’s 

 and member of our advisory board, serves as the moderator for this conversation.

 is an associate professor and transplant nephrologist at Washington University School of Medicine in St. Louis and director of Kidney Transplantation at John Cochran VA Medical Center in St. Louis.

 is a staff nephrologist at the Cleveland Clinic.

 include Otsuka Pharmaceuticals, GSK, Calliditas, and Travere Therapeutics. Relevant disclosures for 

 include Alexion, AstraZeneca, Novartis, Dianthus Therapeutics, Aurinia Pharmaceuticals Inc., Apellis and UptoDate.

 include Vera Therapeutics and Travere Therapeutics.

Apellis Pharmaceuticals. FDA Approves Apellis’ EMPAVELI® (pegcetacoplan) as the First C3G and Primary IC-MPGN Treatment for Patients 12 and Older | Apellis Pharmaceuticals, Inc. Apellis Pharmaceuticals, Inc. Published July 28, 2025. Accessed August 4, 2025. 

https://investors.apellis.com/news-releases/news-release-details/fda-approves-apellis-empavelir-pegcetacoplan-first-c3g-and

Nester CM, Bomback AS, Ariceta G, et al. VALIANT: A Randomized, Multicenter, Double-Blind, Placebo (PBO)-Controlled, Phase 3 Trial of Pegcetacoplan for Patients with Native or Post-transplant Recurrent Glomerulopathy (C3G) or Primary Immune Complex Membranoproliferative Glomerulonephritis (IC-MPGN). 

Journal of the American Society of Nephrology

US Food and Drug Administration. Fabhalta approved for complement 3 glomerulopathy. U.S. Food and Drug Administration. Published March 20, 2025. Accessed August 4, 2025. 

https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-first-treatment-adults-complement-3-glomerulopathy-rare-kidney-disease-reduce

In the final segment of this 5-part HCPLive RX Review, experts discuss real-world barriers to implementing new C3G therapies and lingering unmet needs.

Corey Cavanaugh, DO

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